CHAPTER 71 How Far Have We Come in Prevention and Treatment of Peripheral Neuropathy?

Peter J. Dyck, MD

INTRODUCTION

At a recent conference assessing “Advances in understanding and treating neuropathy” sponsored by National Institute of Neurological Disorders and Stroke,¹ I addressed the question: How far have we come in preventing and treating peripheral neuropathy and from which research disciplines?, which I outline here. The common perception that peripheral neuropathy is a single disease, poorly understood, and in any case, nothing can be done to prevent or treat it, is wrong—very wrong! Peripheral neuropathies occur from many causes; by many presentations, courses, clinical, and anatomic-pathologic patterns; and outcomes vary considerably. Many neuropathies that were commonplace in a former era do not occur today in developed countries. Prevention or treatment is available for more than 50% of them. In a previous report, we described at least 20 anatomic-pathologic patterns of involvement.² Different proximal to distal levels of the peripheral nervous system may be affected, for example, spinal nerve roots, spinal ganglia, and segmental nerves; plexuses (cervical, lumbar or sacral); and proximal to distal levels of nerve trunks. Involvement may selectively affect certain neuron or nerve fiber classes. The pathologic processes may be diverse, ranging from lack of development, neuronal degeneration, distal axonal atrophy and degeneration, axonal dystrophy, and primary and secondary segmental demyelination and regeneration. Because of the symbiosis of Schwann cells and nerve fibers, involvement of one affects the other. The mechanisms underlying neuropathy are generally the same ones affecting other tissue, that is, congenital agenesis or maldevelopment; mechanical injury; hereditary disorders; infection; immune inflammation; medicinal and industrial toxins; and metabolic, vascular, and other causes.

The history of prevention and treatment of peripheral neuropathy is remarkable and the reason for optimism that further advances are possible. Advances have come mainly from improved understanding and treatment of the role of malnutrition and vitamin deficiencies, prevention or treatment of infections, prevention of toxic exposure, treatment of autoimmune disease, and institution of improved public health measures.

The challenge for the future is to prevent or treat primary disease of nerves. Considering their frequency, duration, and severity of morbidity, inherited neuropathies remain a major needed target for research. There is a great need also to identify underlying mechanisms and treatment approaches for such symptoms as weakness; sensory loss leading to neurogenic arthropathy and plantar ulcers; positive neuropathic sensory symptoms of “prickling,” “asleep numbness”—like a hand that has “gone asleep” from lying on it, and “lancinating,” “burning,” and “deep aching” pains; and autonomic symptoms of diverse kinds.

Mechanical injury of nerves

Compression and entrapment of nerves are among the most common neuropathic injuries. Many of these injuries are preventable or treatable. Although diseases of spinal nerve roots are not generally thought of as neuropathies, in a broad sense they are by reason of their myelin investment of nerve fibers by Schwann cells. Nerve root injury commonly relates to disk protrusion or extrusion, and spinal stenosis or more generalized vertebral column disease. Whereas many patients experience immediate pain relief from laminectomy and disk fragment removal, results from randomized controlled trials are few and provide somewhat unclear conclusions.³ Sadly, injury of limb nerves is especially common at this time and relate to war, and automobile and farm accidents. Compression and entrapment of nerves commonly affect the median nerve at the wrist (carpal tunnel syndrome [CTS]), the ulnar nerve at the elbow, the peroneal nerve at the knee, and at other sites and nerves. Much is known about underlying pathophysiology of these disorders and how they can be prevented or treated. To illustrate, effective prevention and treatment of CTS is available, for example, reduction of repetitive motion, transection of the carpal ligament, splinting of the wrist, local injection of corticosteroids, and recognition and treatment of associated underlying metabolic diseases (hypothyroidism, rheumatoid arthritis, and other conditions). In a Cochrane review, it was suggested that “surgical treatment is probably better than splinting, but it is unclear whether it is better than steroid injection.”⁴ Because many nerve injuries relate to war, and automobile and farm accidents, reduction of wars, driving under the influence of alcohol or other mind-altering drugs, and safety design of cars and farm implements are the most important approaches to reducing these neuropathies.

Infection and peripheral neuropathy

Infection may affect nerves by direct invasion of microorganisms or by associated or later immune reactions to such infections. A treatable complication of syphilis, tabes dorsalis, is seldom encountered today in developed countries but was commonplace in earlier times. It was due to an inflammatory reaction of the pia-arachnoid at the root entry zone of dorsal spinal roots into spinal cord (the radicular, as compared to the earlier funicular theory of tabes dorsalis). The introduction of penicillin resulted in this improvement. A second infection of peripheral nerves is leprosy, also occurring less frequently today than at former times. It was a major cause of sensory neuropathy of distal exposed cool regions of the body. The organism has a predilection for Schwann cells. With the introduction of dapsone (a sulfone drug) and other antimicrobial agents, infected patients can be treated in an outpatient setting and later complications such as loss of toes and fingers are preventable.⁵ Herpes zoster (shingles), which can cause serious morbidity for a long time due to pain, is now largely preventable by immunization and can be treated with antiviral drugs. Perhaps the best example of prevention of a virus-induced neuropathy is that of poliomyelitis. Strictly speaking, polio is mainly an infection of the anterior horn region of the spinal cord, but its effect is largely on motor axons, to skeletal muscles. New cases of paralysis from poliomyelitis have almost disappeared from developed countries because the oral vaccine has been extremely effective. Lyme disease causes a distinctive febrile illness, a rash, and a radiculoplexus or polyneuropathy that responds to doxycycline therapy.⁶ Perhaps today the most commonly encountered neuropathy related to an infection is that due to human immunodeficiency virus. Treatment with antiretroviral drugs appears to be decreasing their frequency.

Only gold members can continue reading. Log In or Register to continue